Use of Anabolic Steroids in Patients Who Have HIV/AIDS

Of the 3 orally active anabolic steroids, Oxandrolone has been studied in HIV-infected patients more extensively than has Oxymetholone. Stanozolol is used for the treatment of hereditary angioedema and has not been used for its anabolic effect in this patient population to any great extent. Use of the steroid oxandrolone is associated with significant gains in weight and body cell mass in HIV-positive men who had experienced HIV-related wasting, according to an American study published in the March edition of the Journal of Acquired Immune Deficiency Syndromes. However, although the steroid increased muscle mass, it did not improve endurance and caused side-effects, including an increase in levels of ‘bad’ LDL cholesterol and elevations in liver enzymes. Unintentional loss of just 3% of body weight has been associated with poorer survival in HIV-positive individuals. Although the use of antiretroviral therapy has led to a significant decrease in the prevalence of unintended weight loss, it is still common, even amongst people taking HIV treatment.

One of the earlier studies of Oxandrolone in HIV-infected patients was begun before the introduction of the PIs. Sixty-three HIV-infected men with a loss of body weight greater than 10% were randomized to receive placebo; Oxandrolone, 5 mg/d or Oxandrolone, 15 mg/d. The patients who received 15 mg/d of oxandrolone gained weight throughout the 16-week period, whereas those who received 5 mg/d of Oxandrolone maintained their weight. In contrast, the patients who received placebo continued to lose weight.

In a follow-up study, which has not yet been published, patients were randomized to placebo or to 1 of 3 dosages of Oxandrolone - 20 mg/d, 40 mg/d or 80 mg/d (C. Grunfeld, unpublished data, 1998). The patients in the group who received 40 mg/d had the most statistically significant weight gain. However, both the patients in this group and those who received 80 mg/d showed significant increases in serum levels of liver transaminases.

A study published in 1999 sought to determine whether a regimen of supra physiologic doses of androgen (testosterone) plus an anabolic steroid (Oxandrolone) would improve the LBM and strength gains achieved with progressive resistance exercise in HIV-infected men who had experienced weight loss. A second objective of the study was to determine whether antiretroviral therapy with a PI prevented lean body anabolism.

All subjects in the study participated in supervised progressive resistance exercise for 8 weeks. At the same time, they received testosterone, 100 mg/wk, by intramuscular injection. Twenty-four eugonadal men were then randomized to either placebo or Oxandrolone, 20 mg/d. Twenty-two patients completed the study. The results indicated that compared with patients who received placebo, those who received Oxandrolone experienced improved nitrogen balance (P = .05); increased LBM (P = .005); and increased muscle strength, as judged by either maximum weight lifted (P = .02 to .05) or dynamometry (P = .01 to .05). The results were similar regardless of whether the patients were taking a PI. However, compared with placebo, Oxandrolone was associated with a statistically significant decrease in blood levels of high-den-sity lipoprotein (HDL) cholesterol (P < .001).

Because all patients in the study participated in progressive resistance training and received testosterone, only an additive effect of Oxandrolone versus placebo was being determined. Therefore, the study appears to be valid even though the number of patients enrolled was small. On the other hand, had the design of the study called for dividing the patients into multiple groups, so that not all patients received testosterone or participated in progressive resistance exercise, the number of patients required to reach statistical significance would have been much higher.

The conclusions that can be drawn from the study are that Oxandrolone  20 mg/d, added to a program consisting of both progressive resistance exercise and physiologic doses of testosterone improved the anabolic and functional responses in patients who showed HIV-related weight loss.

Only 1 study of Oxymetholone in HIV-infected patients has been reported. This study was a nonblinded pilot trial that was completed in Germany and reported in 1996. Patients were randomly assigned to receive either Oxymetholone (14 patients) or Oxymetholone plus ketotifen (16 patients). Ketotifen is an H1-receptor antagonist (ie, antihista- mine) that has been shown to block tumor necrosis factor a. The patients receiving the medications under study were compared with 30 matched control patients who met the same inclusion criteria, such as advanced HIV infection and chronic cachexia. On completion of the twelve-week double-blind phase of the study, all the patients were offered the option of remaining on the study for a further twelve weeks and receiving an open label 20mg Oxandrolone dose a day. By the end of this period, there were no differences in weight between patients and liver function ceased to be significantly different from baseline.

Although the investigators note that treatment with the steroid was generally “well tolerated” they note that over 5% of patients had moderate or severe increases in levels of liver enzymes and that “LDL levels decreased and HDL levels increased.”

Anabolic steroids are another experimental treatment for lipodystrophy

Anabolic steroids are another experimental treatment for lipodystrophy as well as a standard treatment for HIV-related wasting. French researchers reported on a man receiving treatment with AZT/3TC who developed a buffalo hump and insulin resistance nine months after beginning treatment. He received intramuscular Testosterone Cypionate biweekly for four months and lost abdominal fat and gained lean muscle mass. Furthermore, studies have found that anabolic steroids produce weight and lean body mass increases in people with HIV-related wasting. Steroids may disguise the visible signs of lipodystrophy rather than stop or reverse loss of fat tissue.

A randomized study of Oxymetholone treatment in 92 individuals with weight loss due to HIV wasting or lipodystrophy found that the anabolic steroid had no impact on total body fat after 16 weeks of follow-up, although weight and muscle increased.

Despite the availability of highly active antiretroviral therapy (HAART), chronic, involuntary weight loss still remains a serious problem for some people living with HIV. Various alterations in energy metabolism and endocrine regulation have been found to cause loss of lean body mass (LBM) and body cell mass (BCM).

Previously studies in HIV-positive men undergoing androgen replacement therapy or treatment with recombinant human growth hormone (rGH) have shown partial restoration of lean body mass, but these treatments have been largely ineffective in eugonadal individuals.

Now researchers from the Universities of Essen and Bonn have shown that the anabolic steroid oxymetholone can be considered an effective treatment for eugonadal male and female patients with AIDS-associated wasting.

A total of 89 patients (79 men and 10 women: 69 gay/bisexual men, 12 intravenous drug users, 7 heterosexual contact, one transfusion recipient) were enrolled

Patients were randomized to receive either 100mg/day twice daily (BID) or 150mg/day three times daily (TID) or placebo for 16 weeks. Patients in the placebo group gained 1.0 kg compared to 3.0kg among those receiving therapy three times daily and 3.5kg among those receiving therapy twice daily.

Seventeen patients (19%) discontinued treatment during the double-blind phase of the study. Fourteen patients (16%) were lost to follow-up or discontinued for personal or unknown reasons. One patient in the Oxymetholone BID arm discontinued due to nausea and vomiting and two patients in the Oxymetholone TID arm discontinued due to elevated liver enzymes.

Significant improvements were noted in appetite and food intake, increased well-being and reduced weakness by self-examination. Recent research has found that higher LBM is significantly associated with better physical functioning and better general health perceptions as well as with fewer days in bed in men, though not in women. The most important adverse event was liver associated toxicity. Overall, 35% of patients in the TID arm, 27% of patients in the BID arm and no patients in the placebo group had a greater than five times baseline increase for alanine aminotransferase during the double-blind phase of the study.

Weight gain was observed after an average of two weeks. The initial increase was rapid until week 4, but body weight remained at the same level from this point on. There was no correlation between the extent of weight gain and age, sex or disease stage.

Only one female developed a self-reported clitoris enlargement, whereas changes in libido were similar across groups. Oxymetholone can be considered an effective anabolic steroid in eugonadal male and female patients with AIDS-associated wasting, with the twice daily 100mg/day regimen appearing equally effective as the three times daily 150mg/day in terms of weight gain, LBM and BCM, as well as being associated with less, but still significant liver toxicity.